Haemoglobinopathies and Obstetric Haematology

Question 1

What two chromosomes do the globin chains come from?

Answer 1

16 and 11

Question 2

What are haemoglobinopathies?

Answer 2

changes in globin genes or their expression leading to a disease

Question 3

What are examples of structural Hb varients?

Answer 3

Hb S (Sickle), C, D, E
usually a single base substitution in globin gene = altered structure and function

Question 4

What are thalassaemias? (on a genetic level)

Answer 4

change in SINGLE globin gene expression leads to reduced rate of synthesis of NORMAL globin chains
due to imbalance of alpha and beta chain production
free globin chains damage red cell membrane

Question 5

What are the anaemia and macrocytosis that occur during pregnancy?

Answer 5

Plasma volume expands in pregnancy by 50%.
MCV increases
Pregnancy also increases folic acid requirements
Haemodilution occurs - maximally at 32 weeks
anaemia - Fe deficiency most common

Question 6

When does leukocytosis occur in pregnancy?

Answer 6

Mainly a neutrophilia

rising from the 2nd month to a peak range of around 9-15 in the 2nd-3rd trimester

Question 7

What is gestational thrombocytopenia and when does it occur?

Answer 7

Platelet count usually >70x109/l
Platelet count falls after 20weeks and thrombocytopenia is most marked in late pregnancy
No pathological significance for mother or fetus
rapid recovary

Question 8

What is meant my ‘consumptive’ causes of thrombocytopenia In pregnancy?

Answer 8

increased platelets are fragmented and consumed

Question 9

What are examples of ‘consumptive’ causes of thrombocytopenia in pregnancy?

Answer 9

Gestational
Pre-eclampsia and HELLP (Hemolysis. Elevated Liver enzymes. Low Platelet count) syndrome
AFLP (acute fatty liver of pregnancy)
DIC eg in abruption
TTP (Thrombotic thrombocytopenic purpura)/HUS (Hemolytic uremic syndrome)

Question 10

What coagulation methods are activated in pregnancy?

Answer 10

increase in platelet activation
imcrease in procoagulant factors
Reduction in some natural anticoagulants
Reduction in fibrinolysis
Rise in markers of thrombin generation
increase in coagulation factors i.e. factors, vWF

Question 11

How are haemoglobinopathies diagnosed?

Answer 11

FBC and film
Structural Hb variants detected by Haemoglobin Electrophoresis
Thalassaemias have normal Hb electrophoresis but small pale red cells

Question 12

How do sickle cells get their shape?

Answer 12

Sickle Hb (Hb-S) polymerises at low oxygen tensions
forms long fibrils (“tactoids”) distort the red cell membrane and produce the classical sickle shape

Question 13

What is Haemolysis-associated haemostatic activation?

Answer 13

occurs when red blood cells essentially ‘burst’
releases haemoglobin into the blood plasma
this combines with NO and produces reactive O2 species
The decrease in NO causes haemostatic activation i.e. platelet activation, tissue factor activation, thrombin and fibrin generation, thrombosis

Question 14

What is the clinical presentation of heterozygous sickle cell anaemia?

Answer 14

no problems except when extreme hypoxia/dehydration

Question 15

What are the acute complications of sickle cell disease?

Answer 15

Vaso-occlusive crisis - hands and feet (dactylitis - inflammation of an entire digit), chest syndrome, abdominal pain (mesenteric), bones (long bones, ribs, spine), brain, priapism - persistent and painful erection of the penis
Septicaemia
Aplastic crisis - temporary cessation of red cell production
Sequestration crisis (spleen, liver)

Question 16

What are the chronic complications of sickle cell disease?

Answer 16

Hyposplenism - due to infarction and atrophy of spleen
Renal disease: can’t concentrate urine (bed-wetting at night), chronic renal failure/dialysis
Avascular necrosis (AVN) –femoral/humeral heads
Leg ulcers
osteomyelitis
gall stones
retinopathy
cardiac
respiratory
Death

Question 17

Are thalassaemias commonly homozygous or heterozygous?

Answer 17

heterogeneous

Question 18

What are the two types of thalassaemias and what is the difference between them both?

Answer 18

α-thalassaemia: involving the genes HBA1 and HBA2, due to impaired production of alpha chains
β-thalassaemia: Reduced rate of production of beta-globin chains, pathology caused by excess alpha chains

Question 19

What are the 3 sub catagories of β-thalassaemia?

Answer 19

Thalassaemia Minor - carriers. Clinically normal
Thalassaemia intermedia
Thalassaemia Major - severe disease which is usually fatal if untreated. produces little, if any, Hb-A

Question 20

What what age does Thalassaemia intermedia present?

Answer 20

4-5 years old

Question 21

What what age does Thalassaemia major present?

Answer 21

1 to 2 years

Question 22

What are the consequences of compensatory increased marrow activity?

Answer 22

skeletal deformity
stunted growth
increased iron absorption
organ damage (exacerbated by blood transfusion)
protein malnutrition

Question 23

What are the consequences of compensatory enlarged and overactive spleen?

Answer 23

pooling of red cells (increased anaemia)

increased transfusion requirement

Question 24

What are the facial feathures of a person with thalassaemia major?

Answer 24

Maxillary hypertrophy - wide jaw
Abnormal dentition - teeth
Frontal bossing - forehead comes forward due to expanded bone marrow

Question 25

What can be seen on an x-ray of a patient with β-thalassaemia major?

Answer 25

“hair on end” skull due
to widening of diploic cavities
by marrow expansion

Question 26

What is the treatment for β-thalassaemia major?

Answer 26

Transfusion every 3-4 weeks from the 1st year of life

Question 27

What is the consequence of using transfusion as the treatment for β-thalassaemia major?

Answer 27

the body has no excretory mechanism for excess iron
by 10-12 years of age there is severe iron overload and toxicity:
gonads/hypothalamus – failure of puberty, growth failure
pancreas – diabetes
heart – dilated cardiomyopathy and heart failure
liver - cirrhosis
transmission of infections
Allo-immunisation - immune response to foreign antigens from members of the same species

Question 28

What is the preventative treatment from death from iron overload?

Answer 28

Iron chelation therapy - from 2nd year of life

Desferrioxamine - 8-12 hourly subcutaneous infusion